Increased Plasma Aldosterone Levels Research Articles

Both low sodium and high potassium intake increase the level of adrenal angiotensin-II receptor type 1, but not that of adrenocorticotropin receptor

Angiotensin-II (AII), a component of the renin-angiotensin system, is the major factor that regulates the formation of aldosterone in the adrenal cortex zona glomerulosa (ZG). The activity of this system is increased by an increase in potassium intake or a decrease in sodium intake. Using immunoblotting analysis, we determined whether these ions affect the expression of type 1 AII receptors (AT1) and compared the results thus obtained with the AT1 receptor mRNA levels. We also studied the interrelation among AII, AT1 receptors, cytochrome P450 aldosterone synthase (P450c18), and plasma aldosterone levels in rats fed a normal diet or a low sodium or high potassium diet with or without captopril, an inhibitor of angiotensin-converting enzyme, for 7 days. The effects of ions on the level of ACTH receptor mRNA were also analyzed. We found that a low sodium intake increased plasma aldosterone levels from 5.5 to 236 ng/dl and led to 2.3- and 3.7-fold increases in the levels of adrenal ZG AT1 receptor protein and AT1 receptor mRNA, whereas a 11.8-fold increase was found in the level of P450c18 mRNA. Captopril almost completely reversed these effects. We have shown that a high potassium intake increased plasma aldosterone levels to 25.9 ng/dl and also led to 1.84- and 1.95-fold increases in the level of ZG AT1 receptor protein and AT1 receptor mRNA, whereas the ZG P450c18 mRNA level was increased 3.5-fold. The plasma aldosterone level of animals fed a high diet of potassium and captopril was still higher than that in control animals at 16.6 ng/dl, and the levels of ZG AT1 receptor and P450c18 mRNAs were only slightly less than those of the high potassium groups, indicating that captopril did not efficiently block aldosterone formation under these conditions. ACTH receptor mRNA levels remain unaffected by either low sodium or high potassium intake. Collectively, these results indicate that the increased aldosterone secretion induced by low sodium or high potassium intake involves concomitant increases in AT1 receptor and P450c18 mRNAs, which are effectively translated into their respective proteins, and that the expression of both proteins is mediated in part by AII.

Heterogeneous changes of serum potassium levels in NIDDM patients on oral glucose load.

Ten noninsulin dependent diabetic patients (NIDDM) without baseline hyperkalemia and with normal aldosterone levels when given 100 g of glucose orally revealed heterogeneous responses in serum potassium changes. Six diabetics had paradoxical increases in serum potassium levels averaged 0.44 mEq/L (range, 0.1 to 1.1 mEq/L) and were accompanied by increases in plasma aldosterone levels. On the contrary, four other noninsulin dependent diabetics and four nondiabetic control subjects had gradual decreases in serum potassium levels with simultaneous decreases in plasma aldosterone levels. These rises and falls in serum potassium concentrations coincided with changes in serum osmolality related mostly to the degree of increases in serum glucose following oral glucose administration. pH of venous blood didn’t show any relevant and significant changes with changes of serum potassium levels following oral glucose load. This finding suggests that osmotic mechanisms with various degree of well known abnormal insulin secretion and resistance to insulin action in target tissues in NIDDM patients may account for these heterogeneous responses in serum potassium changes after glucose load, and normal aldosterone levels may not be sufficient to prevent glucose induced increases in serum potassium in NIDDM patients.

Ammonium chloride metabolic acidosis and the activity of renin-angiotensin-aldosterone system in children

The present study was undertaken to assess the effects of acute metabolic acidosis on the activity of the renin-angiotensin-aldosterone system in 12 children with a mean age of 8.9 years who underwent NH4Cl loading test. Ammonium chloride was given in a dose of 0.15 g/kg per day for 3 consecutive days to evaluate renal acidification. Prior to and following NH4Cl administration blood acid-base parameters, plasma and urine electrolytes, creatinine and aldosterone concentrations as well as plasma renin activity (PRA), urine flow rate and net H+ excretion were measured. Ammonium chloride administration significantly depressed blood pH (P less than 0.05), bicarbonate (P less than 0.01) and base excess (P less than 0.01) and resulted in a slight, but significant elevation of plasma potassium concentration (P less than 0.05). Furthermore, NH4Cl ingestion induced a marked increase in urine flow rate (P less than 0.01) and urinary sodium, potassium and chloride excretion (P less than 0.01). In response to NH4Cl metabolic acidosis, PRA doubled (4.72 +/- 1.18 vs 8.13 +/- 1.02 ng/ml per hour, P less than or equal to 0.05) and there was a nearly four-fold increase in plasma aldosterone level (0.49 +/- 0.12 vs 1.52 +/- 0.24 ng/ml, P less than 0.01) and in urinary aldosterone excretion (19.2 +/- 4.3 vs 71.8 +/- 13.8 micrograms/day, P less than 0.01). The elevated aldosterone production observed in this study is assumed to be mediated by the combined effect of sodium and water diuresis-related increased PRA, hyperkalaemia and the direct stimulation of adrenal steroidogenesis by metabolic acidosis.

Furosemide pharmacokinetics and pharmacodynamics in renal transplantation

Furosemide was administered intravenously to four patients who had undergone renal transplantation in the past and four creatinine clearance--matched control subjects. Both patients who had undergone renal transplant and control subjects displayed similar pharmacokinetic and pharmacodynamic behavior, as assessed by drug delivery to the urine and sodium excretion, respectively. Despite similar degrees of natriuresis, patients who had undergone renal transplantation demonstrated a clear defect in urine potassium excretion. This defect in potassium excretion was not related to altered responsiveness of the renin-angiotensin-aldosterone axis because plasma renin activity increased in a normal fashion after furosemide in both control and transplant subjects. Although the plasma aldosterone response to increases in plasma renin activity was sluggish in patients undergoing renal transplantation, normal increases in plasma aldosterone levels were achieved in both groups, suggesting that there may be an intrinsic defect in distal tubular potassium secretion that can be unmasked by furosemide.

Atrial natriuretic peptide inhibits the effect of endogenous angiotensin II on plasma aldosterone in conscious sodium-depleted rats.

Previous studies have shown that atrial natriuretic peptide (ANP) inhibits the secretion of aldosterone by isolated adrenal glomerulosa cells stimulated by angiotensin II, adrenocorticotropic hormone and potassium in vitro. We have also demonstrated that this inhibitory effect of ANP on plasma aldosterone induced by angiotensin II and adrenocorticotropic hormone can be reproduced in vivo in conscious unrestrained rats. In this study, we have investigated the effect of an intravenous infusion of ANP on plasma aldosterone in conscious unrestrained sodium-depleted rats. During sodium depletion, the rise in plasma renin activity which determines an increment in the circulating concentration of angiotensin II was accompanied by a rise in aldosterone secretion as expected. ANP infused intravenously at a dose which increased the plasma concentration of the peptide three- to five-fold, produced a significant decrement in the concentration of aldosterone in plasma after an infusion period of 120 min. There was no significant effect of ANP on plasma renin activity and plasma corticosterone concentration. Since the increase in plasma aldosterone levels in sodium-depleted rats is mainly dependent on the activation of the renin-angiotensin system, we conclude that ANP may modulate the effect of endogenous as well as exogenous angiotensin II on plasma aldosterone secretion.

Effect of atrial natriuretic factor on the plasma aldosterone response to potassium infusion in rats - in vivo study

Previous in vitro studies have shown that atrial natriuretic factor inhibits the secretion of aldosterone stimulated by AII, ACTH, and potassium in adrenal cell suspensions. The present study investigated the effects of atriopeptin II on the plasma aldosterone response to a potassium infusion in conscious unrestrained rats in vivo. The infusion of potassium chloride solution increased plasma aldosterone level from 20.4 ± 3.7 to 168.4 ± 27.3 ng/dl. The simultaneous administration of atriopeptin II reduced the increase in plasma aldosterone level ((16.0 ± 2.1 to 63.3 ± 10.4 ng/dl). There was no significant difference in the plasma renin activity, corticosterone, or serum potassium levels between the two groups. These results suggest that atriopeptin II may be important in the regulation of aldosterone secretion.

1 Case of Primary Aldosteronism Caused by Adrenal Hyperplasia

Primary aldosteronism is a disease that the stimulus for the excessive aldosterone production resides within the adrenal gland. It was first described by conn in 1955. And many cases were reported by physicians at present in the world. But it is relatively rare in Korea, probably due to lack of attension and medical facilities. Only about 13 cases have been reported at present. The clinical, biochemical features in 1 case of primary aldosteranism caused by adrenal hyperplasia that was diagnosed at Yeungnam University Hospital was observed and the following result were obtained. 1. Clinical feature: The present case was 27-year-old woman who was admitted due to general weakness and easy fatigability. The above mensioned chief complaints occurred 8 months prior to admission when she delivered of second baby by cesarian section. Symptoms such as above chief complaints, intermittent muscle paralysis and cramping were noticed. Trousseau's sign was also present. The average blood pressure ranged from 170/90 to 200/120. 2. Biochemical abnormalities: Severe hypokalemia lower than 2.5 mEq/L was presented and 24 hours urine potassium showed markedly increased urinary loss.(228 mEq/day). Plasma renin activity was decreased under normal range with furosemide administration.(Basal renin; 0.01ng/ml/hr, stimulated renin 0.12ng/ml/hr). Saline suppression test revealed markedly elevated levels of aldosterone higher than normal range. (Basal aldosterone; 320.68pg/ml stimulated aldosterone; 451.86pg/ml). And posture test showed decreased plasma renin activity and increased plasma aldosterone level. - PRA(ng/ml/hr)=Bsal: 0.05(0.15~2.33), Stimulated: 0.22(1.31~3.95) - Aldosterone(pg/ml)=Bsal: 242.77(10~160), Stimulated: 432.09(40~310) 3. Adrenal CT scan revealed no abnormal findings. 4. Treatment and course: Spironolactone was given at OPD with regular follow-up. Her blood pressure ranged from 150/90 to 160/100 and symptoms were improved. The effect of treatment was satisfactory and further follow up would be performed.

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.

Alpha-melanocyte-stimulating hormone stimulation of aldosterone secretion in hypophysectomized rats.

Intact and hypophysectomized male rats on low and high sodium diets were treated with sc infused ACTH and alpha MSH, and the levels of aldosterone and corticosterone were determined in truncal blood. Plasma aldosterone levels were lower in hypophysectomized animals on the low sodium diet than in intact animals on the low sodium diet. Alpha MSH (8 micrograms/day) restored plasma levels of aldosterone to normal in hypophysectomized rats on the low sodium diet. ACTH (6 micrograms/day) did not cause significant changes in plasma levels of aldosterone in hypophysectomized animals. ACTH restored plasma corticosterone to normal in hypophysectomized rats, whereas alpha MSH had no effect on corticosterone. Alpha MSH did not increase plasma aldosterone levels in intact rats. These data suggest that alpha MSH may be important in the regulation of aldosterone secretion in the rat and that zona glomerulosa responsiveness to alpha MSH in vivo is increased by hypophysectomy. The mechanisms of alpha MSH action on glomerulosa cells are different from those of ACTH.

A comparison of the effects of angiotensin II infusion and variations in salt intake on plasma aldosterone levels in normal subjects, patients with essential hypertension and patients with hyperaldosteronism

Infusion of angiotensin II into a patient with dexamethasone-suppressible hyperaldosteronism caused a brisk increase in plasma aldosterone concentration. In this behaviour, the patient resembled those patients with idiopathic hyperaldosteronism rather than those with tumorous primary hyperaldosteronism. Sodium depletion of a small group of patients with mild essential hypertension elicited a spectrum of increases in plasma aldosterone levels ranging from zero to normal. Angiotensin II infusion in both sodium replete and deplete states also caused variable aldosterone responses. These results suggest that the derangement of adrenal function in this condition varies continuously in severity.

Clinical and biochemical features of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism.

Eight patients with aldosterone-producing adenoma (APA) (7 histologically proved) and 6 patients with idiopathic hyperaldosteronism (IHA) (2 histologically proved) were evaluated for differential diagnosis using clinical, radiographic, and biochemical parameters. Mean basal plasma aldosterone (445±146 (SD) pg/ml), 18-hydroxycorticosterone (975±394 pg/ml), and 18-hydroxydeoxycorticosterone levels (374±266 pg/ml) and mean diastolic blood pressure were significantly higher in patients with APA (p<0.05 andp<0.01), whereas mean plasma potassium levels and stimulated plasma renin activity were lower in subjects with APA as compared to patients with IHA (p<0.01 andp<0.01). Radiographic procedures predicted the correct diagnosis in 3 of 8 operated cases (37%) and selective adrenal vein sampling in 5 of 6 cases (83%). Urinary aldosterone excretion (30±10 µg/24 h) was suppressed inall patients with IHA after a 21 isotonic saline infusion in 2 h (13±6,p<0.01). Inall patients with APA, however, aldosterone excretion wasnot suppressible (basal: 36±12). Plasma aldosterone levels of some patients with APA could be reduced by saline infusion and the response was not characteristically different between both groups. After 10 mg metoclopramide iv. the slopes of plasma aldosterone levels were similar for patients with APA and normal subjects. Patients with IHA showed a different secretion pattern with a delay of both the increase and the decline of aldosterone levels. Graded angiotensin II infusions (subpressor doses for normotensive individuals) did not increase plasma aldosterone levels in patients with APA. However, in patients with IHA, excessive increases of aldosterone levels were seen (basal: 268±54 pg/ml, after 4 ng A II/kg−1·min−1: 806±262). From these data, we conclude that patients with APA could be reliably identified before operation by determination of urinary aldosterone before and after a simple saline infusion test. Additionally, plasma aldosterone levels after metoclopramide iv. or angiotensin II infusions may be helpful diagnostic tools.

THE RELATIONSHIP BETWEEN ENDOGENOUS HYPERPROLACTINAEMIA AND PLASMA ALDOSTERONE

It has been suggested that prolactin is a regulator of aldosterone secretion. In order to test this hypothesis, we measured prolactin, thyrotrophin and aldosterone by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in eight normal women before and after the intravenous injection of 200 microgram of thyrotrophin releasing hormone (TRH). Prolactin increased from 4.1 +/- 1.1 ng/ml (mean +/- SE) to a peak of 27.4 +/- 3.8 (P less than 0.005) at 15 min following TRH. Plasma renin activity was not different from control levels (1.0 +/- 0.2 ng/ml/h) during the first hour following the administration of TRH, nor did the plasma aldosterone concentration differ significantly from the control levels (39 +/- 7 pg/ml) during this period. However, with upright posture, an increase in aldosterone (from 31 +/- 3 pg/ml at 1 h to 68 +/- 9 at 2 h, P less than 0.005) and in plasma renin activity (from 0.9 +/- 0.2 ng/ml/h at 1 h to 2.0 +/- 0.5 at 2 h, P less than 0.05) was noted, demonstrating a normal capacity to secrete aldosterone in these subjects. Similarly, no change in aldosterone was seen in nine patients with primary hypothyroidism given TRH, despite the fact that the increase in prolactin was greater than normal. Chronic hyperprolactinaemia was not associated with hyperaldosteronism in six patients with pituitary tumour. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

The effects of angiotensin II blockade in conscious sodium-depleted dogs.

The role of the renin-angiotensin system in the control of the plasma aldosterone concentration was examined during both acute (n = 5) and chronic sodium depletion (n = 12) in conscious dogs. A striking increase in the plasma aldosterone level occurred following ethacrynic acid administration alone but the response was completely blocked by simultaneous infusion of [Sar1, Ala8]- angiotensin II. Plasma renin activity (PRA) increased further and arterial pressure fell during the combination of ethacrynic acid injection and angiotensin analogue infusion. The data are explicable on the basis of angiotensin II as die primary and sole mechanism responsible for the increased plasma aldosterone level. In dogs with chronic sodium depletion, both [Sar1, Ala8]-angiotensin II and the converting enzyme inhibitor SQ 20881 produced a striking fall in the plasma aldosterone concentration and arterial pressure and an increase in PRA; the responses were qualitatively identical for the two blocking agents. Failure of the pl...

Effect of brain stimulation on aldosterone secretion in the rhesus monkey (Macaca Mulatta).

The lateral hypothalamus, and various sites within the limbic system and frontal lobe of the rhesus monkey brain were electrically stimulated using chronically implanted electrodes. A considerble increase in plasma aldosterone levels was observed after stimulation of the lateral hypothalamic area, certain localized sites in the cingulate area, and lower medial parts of the frontal lobe. Inactive sites included most of the amygdala, hippocampus, and basal ganglia, together with other areas within the frontal lobe and cingulate gyrus. Stimulation of all active areas was followed by an increase in plasma renin activity. Plasma cortisol also increased considerably after hypothalamic stimulation but in the case of extra-hypothalamic sites the cortisol response was much less.

Aldosteronoma in a child with localization by adrenal vein aldosterone: Collective review of the literature

Hyperaldosteronism due to aldosteronoma is a rare but potentially curable form of pediatric hypertension. We have presented a patient who had symptoms of enuresis and fatigue, and in whom the diagnosis was suggested by low serum potassium and persistent hypertension. Diagnosis was confirmed by increased plasma and urinary aldosterone and decreased plasma renin. The tumor was localized with the aid of adrenal venography and catheterization, which showed greatly increased plasma aldosterone levels in the right adrenal vein. The pathologic findings were totally reversed by right adrenalectomy. The clinical picture and results following surgical removal of aldosterone-producing tumors in six children are reviewed.

Syndrome of hyporeninemic hypoaldosteronism and hyperkalemia in renal disease.

Four patients presented with hyperkalemia and were found to have mild to marked chronic non-oliguric renal failure, normal diastolic blood pressure, mild hyperchloremic acidosis and impaired renal conservation of sodium during sodium restriction. The hyperkalemia was corrected by exogenous mineralocorticoids. Plasma renin activity and concentration, renin substrate, plasma aldosterone and cortisol were measured. Subnormal levels of plasma renin activity and concentration and of plasma aldosterone were found with diminished responses to upright posture, sodium restriction and exogenous catecholamines. Infusions of angiotensin or ACTH consistently caused modest increases in plasma aldosterone levels. Plasma renin substrate, plasma cortisol and urinary 17-OH-corticosteroids were normal. The data indicate that the hyperkalemia was caused by selective hypoaldosteronism secondary to failure of the renin-angiotensin system. It is postulated that possible factors contributing to this syndrome are structural or fu...